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合成豆甾醇衍生物对体外神经细胞中单纯疱疹病毒复制的抗病毒作用。

Antiviral action of synthetic stigmasterol derivatives on herpes simplex virus replication in nervous cells in vitro.

作者信息

Petrera Erina, Níttolo Analía G, Alché Laura E

机构信息

Laboratorio de Virología, Departamento de Química Biológica, IQUIBICEN, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.

出版信息

Biomed Res Int. 2014;2014:947560. doi: 10.1155/2014/947560. Epub 2014 Jul 24.

DOI:10.1155/2014/947560
PMID:25147828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4131461/
Abstract

Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.

摘要

多官能化豆甾醇衍生物，(22S,23S)-22,23-二羟基豆甾-4-烯-3-酮（化合物1）和(22S,23S)-3β-溴-5α,22,23-三羟基豆甾烷-6-酮（化合物2），可抑制单纯疱疹病毒1型（HSV-1）在源自眼组织的人上皮细胞中的复制和传播。当以不同治疗方式给药时，这两种化合物均可降低疱疹性基质性角膜炎小鼠模型中病变的发生率和严重程度。由于HSV-1引起的脑炎是另一种病毒源性免疫病理学疾病，我们在此评估这两种化合物对HSV-1感染的神经细胞系的抗病毒作用及其抗炎作用。我们发现，这两种豆甾醇衍生物在检测的三种神经细胞系中均表现出低细胞毒性。关于抗病毒活性，在所有情况下，这两种化合物在感染后添加时均可阻止HSV-1增殖以及病毒传播。此外，这两种化合物均能够抑制HSV-1感染Neuro-2a细胞诱导的白细胞介素-6和干扰素-γ分泌。我们得出结论，化合物1和2在HSV-1感染的神经细胞系中发挥了双重抗病毒和抗炎作用，这使其成为值得进一步研究的有趣分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/ee8301ee5954/BMRI2014-947560.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/d56903eb737f/BMRI2014-947560.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/d8b5e3b30a01/BMRI2014-947560.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/c4dcdb14e39e/BMRI2014-947560.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/b9e07551bf96/BMRI2014-947560.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/ee8301ee5954/BMRI2014-947560.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/d56903eb737f/BMRI2014-947560.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/d8b5e3b30a01/BMRI2014-947560.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/c4dcdb14e39e/BMRI2014-947560.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/b9e07551bf96/BMRI2014-947560.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c95/4131461/ee8301ee5954/BMRI2014-947560.005.jpg

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